The heart is the center of a person's circulatory system. It includes an electro-mechanical system performing two major pumping functions. The left portions of the heart draw oxygenated blood from the lungs and pump it to the organs of the body to provide the organs with their metabolic needs for oxygen. The right portions of the heart draw deoxygenated blood from the organs and pump it into the lungs where the blood gets oxygenated. The body's metabolic need for oxygen increases with the body's physical activity level. The pumping functions are accomplished by contractions of the myocardium (heart muscles). In a normal heart, the sinoatrial node, the heart's natural pacemaker, generates electrical impulses, known as action potentials, that propagate through an electrical conduction system to various regions of the heart to excite myocardial tissues in these regions. Coordinated delays in the propagations of the action potentials in a normal electrical conduction system cause the various regions of the heart to contract in synchrony such that the pumping functions are performed efficiently.
A blocked or otherwise damaged electrical conduction system causes the myocardium to contract at a rhythm that is too slow, too fast, and/or irregular. Such an abnormal rhythm is generally known as arrhythmia. Arrhythmia reduces the heart's pumping efficiency and hence, diminishes the blood flow to the body. One type of arrhythmia is fibrillation, where the heart quivers instead of beating normally. For instance, atrial fibrillation (AF) is associated with an abnormal heart rhythm where the atria quivers. AF as a disease target represents a significant unmet need with a hospitalization growth rate of 16.7% over last 5 years. AF-related hospitalization charges contribute over $3 B annually to health care system expenditures. Treatments for arrhythmias include electrical therapy such as pacing and defibrillation therapies, ablation and drug therapies. Catheter based therapies for AF are destructive, dangerous, and highly variable. For example, the procedure takes on the average about 4 hours, and has at best 50-80% efficacy. Drug therapy has approximately 60% efficacy and sometimes is proarrhythmic. Moreover, preventive device therapy has been ineffective at suppressing atrial arrhythmias, and shocks are painful device-based therapy that has impacted patient acceptance of implantable cardiac devices (ICD's) both for atrial and ventricular defibrillation.